2001 Fiscal Year Final Research Report Summary
Structure and Function of Antitumor Ligand-Protein Complex Natural Products
| Project/Area Number |
11308022
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bioorganic chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
HIRAMA Masahiro Tohoku University, Department of Chemistry, Graduate School of Science, Professor, 大学院・理学研究科, 教授 (30165203)
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| Project Period (FY) |
1999 – 2001
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| Keywords | Protein Complex / C-1027 / Antitumor Antibiotic / Chromophore / Apoprotein / benzyne / biradical / ESR |
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| Research Abstract |
A number of extremely potent enediyne antitumor antibiotics have been isolated from culture filtrates of Streptomyces species. Although these antibiotics are believed to generate p-benzyne-type biradicals through cycloaromatization, no direct EPR measurements of carbon radical species generated from enediyne antibiotics have been reported. A chromoprotein antibiotic, C-1027, which is powder of a 1 : 1 complex composed of a carrier apoprotein and a DNA cleaving enediyne chromophore, shows a steady EPR spectrum at room temperature. We characterized three paramagnetic species existing in C1027 antibiotic by EPR spectroscopy. These radical species are supplied constantly by dynamic processes through hydrogen abstraction by p-benzyne type biradical from the apoprotein. The present results provide strong evidence for equilibration between the enediyne and p-benzyne form, as well as a chemical mechanism of deterioration leading to self-inactivation of the C-1027 antibiotic.
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Research Products
(42 results)
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[Publications] M.Hirama, K.Akiyama, T.Tanaka, T.Noda, K.Iida, I.Sato, R.Hanaishi, S.Fukuda-Ishisaka, M.Ishiguro, T.Otani, J.E.Leet: "Paramagnetic Enediyne Antitumor Antibiotic C-1027 : Spin Identification and Characterization of Radical Species"J. Am. Chem. Soc.. 122. 720-721 (2000)
Description
「研究成果報告書概要(欧文)」より
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